title: Ciprofloxacin prevents myelination delay in neonatal rats subjected to E. coli sepsis.
abstract: OBJECTIVE
  Perinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti-inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis.
  
  
  METHODS
  We adapted an Escherichia coli sepsis model to 5-day-old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory-induced brain damage compared with cefotaxime (CTX) (treatment of reference).
  
  
  RESULTS
  Compared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX.
  
  
  CONCLUSIONS
  These data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis-induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale AVENIR, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Gauthier
authors.initials: G
authors.lastname: Loron
authors.forename: Paul
authors.initials: P
authors.lastname: Olivier
authors.forename: Hélène
authors.initials: H
authors.lastname: See
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Le Saché
authors.forename: Leslie
authors.initials: L
authors.lastname: Angulo
authors.forename: Valérie
authors.initials: V
authors.lastname: Biran
authors.forename: Nadège
authors.initials: N
authors.lastname: Brunelle
authors.forename: Bernadette
authors.initials: B
authors.lastname: Besson-Lescure
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Kitzis
authors.forename: Julien
authors.initials: J
authors.lastname: Pansiot
authors.forename: Edouard
authors.initials: E
authors.lastname: Bingen
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bonacorsi
authors.forename: Olivier
authors.initials: O
authors.lastname: Baud
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003711:Demyelinating Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004927:Escherichia coli Infections / Q000150:complications* / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000378:metabolism; D018805:Sepsis / Q000150:complications* / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D000890:Anti-Infective Agents; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C506913:Sema3F protein, rat; D040121:Semaphorin-3A; D002939:Ciprofloxacin; D052247:Nitric Oxide Synthase Type II